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Background/aims: Primary radiation therapy is used to treat malignant uveal melanoma (UM). We report our single-centre experience with fractionated radiosurgery (fSRS) with a linear accelerator (LINAC) after specific adaptation for small target volumes with HybridArc., Methods: From October 2014 to January 2020, 101 patients referred to Dessau City Hospital with unilateral UM underwent fSRS with 50 Gy given in five fractions on five consecutive days. Primary endpoints were local tumour control, globe preservation, metastasis and death. Potential prognostic features were analysed. Kaplan-Meier analysis, Cox proportional hazards model and linear models were used for calculations., Results: The median baseline tumour diameter was 10.0 mm (range, 3.0-20.0 mm), median tumour thickness 5.0 mm (range, 0.9-15.5 mm) and median gross tumour volume (GTV) 0.4 cm³ (range, 0.2-2.6 cm³). After a median follow-up of 32.0 months (range, 2.5-76.0 months), 7 patients (6.9%) underwent enucleation: 4 (4.0%) due to local recurrence and 3 (3.0%) due to radiation toxicities, and 6 patients (5.9%) revealed tumour persistence with a GTV exceeding 1.0 cm³. Of 20 patients (19.8%) who died, 8 (7.9%) were tumour-related deaths. Twelve patients (11.9%) suffered from distant metastasis. GTV showed an impact on all endpoints, and treatment delay was associated with reduced odds of eye preservation., Conclusion: LINAC-based fSRS with static conformal beams combined with dynamic conformal arcs and discrete intensity-modulated radiotherapy results in a high tumour control rate. The tumour volume is the most robust physical prognostic marker for local control and disease progression. Avoiding treatment delay improves outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Antibiotic resistance is emerging as a global public threat. However, it remains poorly investigated in the context of periodontal therapy. The aim of the study was to investigate the complete diversity of antibiotic resistance genes in a German population., Methods: Thirty-nine volunteers with periodontitis contributed to the present study with one to four periodontal pockets for a total of 124 subgingival samples. Samples were analyzed using shotgun metagenomics., Results: A total of 19 antibiotic resistance genes from six antibiotic classes were detected in subgingival biofilm. Two thirds of the volunteers (n = 26/39) showed antibiotic resistance genes for at least one of the antibiotic classes used for periodontal treatment in dental practice or research: beta-lactam, lincosamide, macrolide, nitroimidazole, and tetracycline. Macrolide was the most abundant class detected (21/39 patients)., Conclusions: Findings from our study suggest a high prevalence of antibiotic resistance genes in periodontal pockets from German volunteers. We recommend the development and broader use of molecular diagnostic tests for antibiotic resistance in dental practice to ensure treatment success and to minimize antibiotic resistance., (© 2023 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Inflammatory periodontal and peri-implant diseases follow dysbiotic shifts in a susceptible host. A well-established tool for microbial sample collection is the use of paper points. The purpose of this pilot study was to evaluate the use of interdental brushes compared to paper points. Biofilm samples were collected with paper points and later interdental brushes from ten patients. Five patients were represented with a community periodontal index of treatment needs (CPITN) of 0-2 around the teeth and an implant with PPD ≤ 5 mm and no radiological bone loss. The remaining five patients had a CPITN ≥ 3 and one implant with peri-implantitis. Microbial samples were analyzed with quantitative polymerase chain reaction (qPCR) and next-generation sequencing (NGS). The results showed higher amounts of DNA in samples taken by interdental brushes but also higher Ct values. Both methods detected Filifactor alocis , Porphyromonas gingivalis , Prevotella intermedia , Tannerella forsythia, and Treponema denticola in the majority of samples, while Aggregatibacter actinomycetemcomitans was rarely found. A microbial dysbiosis index showed comparable or higher values in sites with no periodontitis/peri-implantitis with interdental brushes. The results of this pilot study indicate that interdental brushes might be a valid technique for microbial sampling and particularly advantageous in the early detection of dysbiotic shifts around teeth and implants. Larger studies with more participants are needed to validate the proposed microbial sampling method with interdental brushes.

Background: ALK receptor tyrosine kinase (ALK) aberrations have an established role in pathogenesis of many neoplasms, but their clinical significance in high grade serous ovarian carcinoma (HGSOC) is unclear., Objective: To analyse the frequency of ALK overexpression, molecular abnormalities of ALK, and their impact on the progression-free survival (PFS) and overall survival (OS) in HGSOC., Methods: Protein expression was examined by immunohistochemistry (IHC) using three different clones of anti-ALK antibody. The presence of translocations was analysed using fluorescent in situ hybridization. Next-generation sequencing was used for studying the copy number variation, as well as point mutation and translocations involving other commonly rearranged genes., Results: ALK overexpression was demonstrated in up to 52% of tumours, whereas ALK copy gains in 8.2%, with no clear impact on survival. ALK point mutations were identified in 13 tumours (8.9%), with 3 belonging to the class IV showing significantly better OS. A trend suggesting better PFS was also noticed in these cases. Additionally, three gene fusions were found: ERBB2-GRB7, PRKCA-BRCA1 and SND1-BRAF, none of which has been previously described in HGSOC., Conclusions: HGSOC harbouring activating ALK mutations might be associated with a better survival, while ALK overexpression and ALK amplification does not impact the prognosis.

The phenotypic expression of antibiotic resistance genes (ARGs) can hamper the use of antibiotics as adjuncts to subgingival instrumentation in the treatment of periodontitis patients. The aim of the study was to analyze the relationship between the phenotypic and genotypic resistance against ampicillin-sulbactam, clindamycin, doxycycline and metronidazole of subgingival biofilm samples from 19 periodontitis patients. Samples were analyzed with shotgun sequencing and cultivated anaerobically for 7 days on microbiological culture media incorporating antibiotics. All growing isolates were identified to the species level using MALDI-TOF-MS and sequence analysis of the 16S ribosomal RNA (rRNA) gene. Phenotypic resistance was determined using EUCAST-breakpoints. The genetic profile of eight patients matched completely with phenotypical resistance to the tested antibiotics. The positive predictive values varied from 1.00 for clindamycin to 0.57 for doxycycline and 0.25 for ampicillin-sulbactam. No sample contained the nimI gene. It can be concluded that antibiotic resistance may be polygenetic and genes may be silent. Every biofilm sample harboring erm genes was phenotypic resistant. The absence of cfx and tet genes correlated to 100%, respectively, to 75%, with the absence of phenotypic resistance. The absence of nimI genes leads to the assumption that constitutive resistance among several species could explain the resistance to metronidazole.

Purpose: To determine the impact of experimentally preformed peri-implant crater-shaped bone defects on the evolution of in situ microbiota and development of bone defects compared to those induced over time by ligature placement only., Methods: Implants were installed in the mandibles of eight dogs. Standardized bone defects were preformed in four test animals but not in the other four control animals, prior to implant (3.3 mm × 8 mm) installation. After 2 months of healing, peri-implantitis was induced with silk ligatures in both groups for 2 months. Microbial samples were obtained from implants and teeth for analysis at three time points (qPCR), and the average depths of the bone defects were measured., Results: At the baseline, the total marker load of periodontal-pathogenic bacteria (TML) for teeth accounted for 5.2% (0-17.4%). After implant healing, TMLs for implants and teeth were comparable (7.1% [0.3-17.4%]). The TML of both groups was 3.5%, 2 months after ligature placement. Bone defects had a mean depth of 1.84 mm at preformed defects and 1.64 mm at control sites (P > 0.05)., Conclusion: Preformed defects in the test group showed comparable results to the control group in terms of TML, the incidence of periodontal-pathogenic bacteria, and bone defect depth.

Background: Salvage radiation therapy (SRT) can be offered to patients with relapsing glioblastoma multiforme (GBM). Here we report our experience with a schedule extending the treatment time of SRT with the aim to prolong the cytotoxic effect of ionizing radiation while minimizing the cytotoxic hazards for the surrounding brain., Methods and Patients: From 2009 until 2017, 124 of 218 patients received radical resection, adjuvant chemo-radiation with photons and temozolomide (TMZ) followed by adjuvant TMZ. Re-irradiation was performed in 26 patients due to local relapse. Treatment schedules varied. Survival and molecular markers were assessed., Results: The median survival was respectively 12 months (9-14.5) of the 124 patients treated with tri-modal therapy and 19.2 months (14.9-24.6) for the 26 patients retreated with SRT ( p =0.038). Patients who received daily fractions of 1,6 to 1,65 Gy to a total dose of >40 Gy had a median survival time of 24,6 months compared to patients treated with higher daily doses or a total dose of <40 Gy (p= 0.039), consistent with the observation that patients treated with 21-28 fractions had a median survival of 21,9 months compared to 15,8 months of patients who received 5-20 fractions (p=.0.05). Patients with Ki-67 expression of >30% seemed to perform better than patients with expression levels of ≤20% ( p =0.03). MGMT methylation status, TERT promoter or ATRX mutations, overexpression of p53, p16, PD-L1, and EGFR were not prognostic., Conclusions: Re-irradiation of relapsing GBM is a highly valid treatment option. Our observation challenges hypofractionated stereotactic radiotherapy for retreatment and controlled trials on the fractionation dose for SRT are needed. Robust predictive molecular markers could be beneficial in the selection of patients for SRT., Competing Interests: Author YG was employed by PathoNext GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Ciernik, Gager, Renner, Spieker, Arndt and Neumann.)

To evolve and to be maintained, seasonal migration, despite its risks, has to yield fitness benefits compared with year-round residency. Empirical data supporting this prediction have remained elusive in the bird literature. To test fitness related benefits of migration, we studied a partial migratory population of European blackbirds ( Turdus merula ) over 7 years. Using a combination of capture-mark-recapture and radio telemetry, we compared survival probabilities between migrants and residents estimated by multi-event survival models, showing that migrant blackbirds had 16% higher probability to survive the winter compared to residents. A subsequent modelling exercise revealed that residents should have 61.25% higher breeding success than migrants, to outweigh the survival costs of residency. Our results support theoretical models that migration should confer survival benefits to evolve, and thus provide empirical evidence to understand the evolution and maintenance of migration.

A fundamental condition for any work with free-ranging animals is correct species identification. However, in case of bats, information on local species assemblies is frequently limited especially in regions with high biodiversity such as the Neotropics. The bat genus Molossus is a typical example of this, with morphologically similar species often occurring in sympatry. We used a multi-method approach based on molecular, morphometric and acoustic information collected from 962 individuals of Molossus bondae, M. coibensis, and M. molossus captured in Panama. We distinguished M. bondae based on size and pelage coloration. We identified two robust species clusters composed of M. molossus and M. coibensis based on 18 microsatellite markers but also on a more stringently determined set of four markers. Phylogenetic reconstructions using the mitochondrial gene co1 (DNA barcode) were used to diagnose these microsatellite clusters as M. molossus and M. coibensis. To differentiate species, morphological information was only reliable when forearm length and body mass were combined in a linear discriminant function (95.9% correctly identified individuals). When looking in more detail at M. molossus and M. coibensis, only four out of 13 wing parameters were informative for species differentiation, with M. coibensis showing lower values for hand wing area and hand wing length and higher values for wing loading. Acoustic recordings after release required categorization of calls into types, yielding only two informative subsets: approach calls and two-toned search calls. Our data emphasizes the importance of combining morphological traits and independent genetic data to inform the best choice and combination of discriminatory information used in the field. Because parameters can vary geographically, the multi-method approach may need to be adjusted to local species assemblies and populations to be entirely informative.

Background: The relationships between group size, survival, and longevity vary greatly among social species. Depending on demographic and ecological circumstances, there are both positive and negative effects of group size variation on individual survival and longevity. For socially foraging species in particular there may be an optimal group size that predicts maximum individual survival that is directly related to the potential for information transfer, social coordination, and costs of conspecific interference. Our aim was to investigate this central aspect of evolutionary ecology by focusing on a socially foraging bat, Molossus molossus. This species optimizes foraging success by eavesdropping on the echolocation calls of group members to locate ephemeral food patches. We expected to find the highest survival and longest lifespans in small groups as a consequence of a trade-off between benefits of information transfer on ephemeral resources and costs of conspecific interference., Results: In a mark-recapture study of 14 mixed-sex M. molossus social groups in Gamboa, Panama, spanning several years we found the expected relatively small and intermediate, but stable groups, with a mean size of 9.6 ± 6.7 adults and juveniles. We estimated survival proxies using Cox proportional hazard models and multistate-mark recapture models generated with recapture data as well as automated monitoring of roost entrances in a subset of the groups. Median survival of females was very short with 1.8 years and a maximum estimated longevity of 5.6 years. Contrary to our expectations, we found no relationship between variation in group size and survival, a result similar to few other studies., Conclusions: Strong selection towards small group size may result from psychoacoustic and cognitive constraints related to acoustic interference in social foraging and the complexity of coordinated flight. The short lifespans were unexpected and may result from life at the energetic edge due to a highly specialized diet. The absence of a relationship between group size and survival may reflect a similar but optimized survival within the selected range of group sizes. We expect the pattern of small group sizes will be consistent in future research on species dependent on social information transfer about ephemeral resources.

Sequences of the mitochondrial cytochrome b (1140 bp) and nuclear Rag 2 (1148 bp) genes were used to assess the evolutionary history of the cosmopolitan bat genus Myotis, based on a worldwide sampling of over 88 named species plus 7 species with uncertain nomenclature. Phylogenetic reconstructions of this comprehensive taxon sampling show that most radiation of species occurred independently within each biogeographic region. Our molecular study supports an early divergence of species from the New World, where all Nearctic and Neotropical species plus a lineage from the Palaearctic constitute a monophyletic clade, sister to the remaining Old World taxa. The major Old World clade includes all remaining Eurasian taxa, most Oriental species, one Oceanian, and all Ethiopian species. Another lineage, including M. latirostris from Taiwan, appears at the base of these two major biogeographic clades and, because it bears nyctalodont molars, could be considered as a distinct genus. However, this molar configuration is also found in crown-group species, indicating that these dental characters are variable in the genus Myotis and may confound interpretation of the fossil record. Molecular datings suggest an origin of all recent Myotis in the early Miocene (about 21MYA with 95% highest posterior density interval 23-20MYA). This period was characterized by a global climatic cooling that reduced the availability of tropical habitats and favoured the development of more temperate vegetation. This sharp climatic change might have triggered the evolution of Myotis in the Northern continents, because Myotis ancestors seem to have been well adapted and successful in such temperate habitats. Ancestral area reconstructions based on the molecular phylogeny suggest that the eastern portion of the Asian continent was an important center of origin for the early diversification of all Myotis lineages, and involved relatively few subsequent transcontinental range expansions., (Copyright © 2013 Elsevier Inc. All rights reserved.)